Accelerated cognitive decline in adult survivors of pediatric central nervous system (CNS) tumors: A report from the Childhood Cancer Survivor Study (CCSS).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10049-10049
Author(s):  
Nicholas Steve Phillips ◽  
Kayla Stratton ◽  
AnnaLynn M. Williams ◽  
Wei Liu ◽  
Tim Ahles ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Group Treatment ◽  
Emotional Regulation ◽  
Chronic Conditions ◽  
Linear Models ◽  
Adult Survivors ◽  
Elevated Risk ◽  
Cns Tumors ◽  
Cns Tumor ◽  
Task Efficiency

10049 Background: Survivors of pediatric CNS tumors may be at elevated risk for accelerated cognitive decline as they age through adulthood relative to the general population, which may be an early risk factor for dementia. Methods: Longitudinal analysis of 512 CNS tumor survivors (52.3% female, mean [SD] 30.6 [7.1] years at T1) and 232 siblings (57.8% female, mean [SD] 34.2 [8.4] years at T1) from the CCSS was conducted using the Neurocognitive Questionnaire (NCQ) to assess task efficiency, emotional regulation, organization and memory at two timepoints separated by a mean of 11.6 [0.7] years. Impairment in each NCQ domain was defined as a score ≥ 90th percentile of the CCSS sibling distribution at each survey, with decline defined as moving from unimpaired at T1 to impaired at T2. Treatment exposures were abstracted from medical records. Chronic health conditions were self-reported at T1 and graded according to CTCAE v4.3. Relative risk of decline for group, treatment and chronic condition predictors was estimated using generalized linear models with robust variance estimates. Mediation analysis examined direct effects of treatments and mediating effects of chronic conditions. All models were adjusted for age, sex, and race. Results: At T1, survivors demonstrated higher frequency of impaired memory (24.5% vs. 6.5%, p < 0.001), emotional regulation (14.3 % vs. 5.6%, p < 0.001), task efficiency (43.3% vs. 13.8%, p < 0.001) and organization (17.7% vs. 10.8%, p = 0.015) than siblings. Among those unimpaired at T1, more survivors vs. siblings declined in memory (34.7% vs. 7.8; RR 4.2, 95% CI 2.6-6.9), emotional regulation (15.5% vs. 5.0%; RR 2.8, 95% CI 1.5-5.3), task efficiency (22.7% vs. 7.0%; RR 2.9, 95% CI 1.7-5.2), and organization (14.5% vs. 2.9%; RR 4.9, 95% CI 2.1-11.0) by T2. Decline in survivor memory was associated with exposure to craniospinal irradiation (RR 1.9, 95% CI 1.3-2.8) and focal irradiation (RR 1.6, 95% CI 1.1-2.3) compared with no radiation, and exposure to Ara-C (RR 1.7, 95% CI 1.0-2.8) and cyclophosphamide (RR 1.7, 95% CI 1.01-2.8). Independent of therapy, serious/disabling or life-threatening cardiopulmonary conditions at T1 predicted future decline in memory (RR 1.5, 95% CI 1.02-2.2) and organization (RR 2.0, 95% CI 1.1-3.6), with the presence of 2 or more cardiopulmonary conditions associated with even higher risk (memory RR 2.6, 95% CI 2.0-3.1; organization RR 3.4, 95% CI 1.1-10.5). Chronic conditions did not mediate associations between treatment exposures and cognitive decline. Conclusions: CNS tumor survivors are at elevated risk for impairment and accelerated cognitive decline compared to siblings. Cranial radiation, Ara-C, cyclophosphamide, and cardiopulmonary morbidity are risk factors for decline. Survivors with these exposures/conditions may benefit from interventions to prevent additional future cognitive decline.

scholarly journals Prevalence and Predictors of Neurocognitive Impairment in Long-Term Survivors of Childhood Hodgkin Lymphoma: A Report from the Childhood Cancer Survivor Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 14-15
Author(s):  
Annalynn M Williams ◽  
Mengqi Xing ◽  
Sedigheh Mirzaei Salehabadi ◽  
Yutaka Yasui ◽  
Matt J. Ehrhardt ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Emotional Regulation ◽  
Neurocognitive Impairment ◽  
Elevated Risk ◽  
Chronic Health Conditions ◽  
Health Conditions ◽  
Chronic Health ◽  
Childhood Cancer Survivor Study ◽  
Task Efficiency ◽  
Long Term Survivors

Background: Long-term survivors of childhood Hodgkin lymphoma (HL) are at significant risk for cardiovascular, pulmonary, and endocrine morbidity in addition to subsequent cancers. Emerging evidence suggests that HL survivors may also experience persistent neurocognitive impairment, however the prevalence of neurocognitive impairment has not been well characterized. Further, little work has been done to examine how specific treatments or comorbidities are associated with these impairments. Methods: The current study included 1,760 survivors (52.0% female, mean[sd] 37.5 [6.0] years old, 23.6 [4.7] years from diagnosis) of childhood Hodgkin lymphoma and 3,180 sibling controls (54.5% female, 33.2 [8.5] years old) from the Childhood Cancer Survivor Study. Participants completed questionnaires assessing four domains of neurocognitive impairment (task efficiency, emotional regulation, organization, and memory). Impairment for each domain was defined as a score worse than the 90th percentile of community controls. Treatment exposures were abstracted from the medical record. Second malignancies (SMN) were self-reported and subsequently confirmed by pathology findings or medical record review. Chronic health conditions were self-reported and systematically graded according to the NCI CTCAE v4.3 (Grade 1 mild, Grade 2 moderate, Grade 3 severe/disabling, Grade 4 life-threatening). Generalized estimating equations were used to calculate risk of impairment in survivors compared with siblings adjusted for age, sex, and race. Among HL survivors, multivariable log-binomial regression was used to calculate risk of impairment associated with demographic, clinical, and treatment factors. Separate models examined risk associated with Grade 2+ chronic health conditions adjusted for age, sex, and race. Results: 10.8% of HL survivors reported impaired task efficiency (vs. 7.7% in siblings), 16.6% emotional regulation (vs. 11.5% in siblings), 12.1% organization (vs. 10.3% in siblings), and 8.1% memory (vs. 5.7% in siblings). Compared with siblings, survivors reported significantly higher risk of impairment in each of the four neurocognitive domains after adjusting for age, sex, and race (Table). Female survivors had elevated risk of impairment on emotional regulation (RR [95%CI] 1.4 [1.1,1.9)) and memory (2.0 [1.3,3.0]). Compared with white survivors (91.8% of the population), non-white survivors had higher risk of impairment in task efficiency (2.1 [1.2, 3.5]) and emotional regulation (1.7 [1.0,2.7]). Current smokers (12.3%) had higher risk of impairment in task efficiency (1.9 [1.2, 3.1]), emotional regulation (2.5 [1.7,3.7]), and memory (1.7 [1.0,3.0]). Having a late-relapse (&gt;5 years from diagnosis) or a second malignancy (20.0%) was associated with elevated risk of impairment in task efficiency (1.6 [1.06,2.3]). While not statistically significant, anthracycline exposure (39.8%) was associated with higher risk of impairment in task efficiency (1.3 [0.7,2.2]) and memory (1.6 [0.9,3.0]). No statistically significant associations were noted for bleomycin, corticosteroids, or chest radiation. HL survivors with pulmonary morbidity (8.5%) had a higher risk of impairment on task efficiency (1.9 [1.2,3.0]) compared to those without. Cardiovascular conditions (32.9%) were associated with elevated risk of impairment in all domains (RR range from 1.5 to 2.1, all p&lt;0.05, Table). Endocrine (54.3%) and neurologic conditions (6.6%) were associated with an increased risk of task efficiency, emotional regulation, and memory impairments (RR range from 1.4 to 5.5, all p&lt;0.05, Table). Conclusions: Survivors experienced significantly more neurocognitive impairment compared to sibling controls. Among survivors, potentially modifiable risk factors such as smoking and chronic health conditions were associated with neurocognitive impairment while treatment exposures showed little association. Mitigation or prevention of smoking and chronic health conditions may improve neurocognitive functioning in HL survivors Table Disclosures No relevant conflicts of interest to declare.

Neurocognitive outcomes in adult survivors of neuroblastoma: A report from the Childhood Cancer Survivor Study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 11563-11563
Author(s):  
Caroline Hesko ◽  
Wei Liu ◽  
Deokumar Srivastava ◽  
Tara M. Brinkman ◽  
Lisa Diller ◽  
...  
Keyword(s):  
At Risk ◽  
Hearing Loss ◽  
Emotional Regulation ◽  
Adult Survivors ◽  
Neurocognitive Impairment ◽  
Age At Diagnosis ◽  
Neurocognitive Outcomes ◽  
Childhood Cancer Survivor Study ◽  
Task Efficiency ◽  
Long Term Survivors

11563 Background: Long-term survivors of neuroblastoma may be at risk for neurocognitive impairment due to young age at diagnosis and intensive multimodal therapies. Methods: 837 survivors of neuroblastoma (57% female; median [range] age 25 [17-58] years, age at diagnosis 1 [0-21] years) and 728 siblings (56% female; age 32[16-43] years) self-reported neurocognitive problems using a neurocognitive questionnaire. Impairment was defined as scores ≥90th percentile of siblings in emotional regulation (ER), organization, task efficiency (TE), and memory. Multivariable log-binomial models evaluated associations with treatment exposures, era and chronic conditions (Grade 2-4 CTCAE v5) adjusting for sex, age, and race. Analyses were stratified by age at diagnosis (≤1 and > 1 year) as proxy for risk group. Results: Rates of impairment were 19.7% (ER), 25.3% organization, 21.9% TE and 19.4% for memory. Survivors had 50% higher risk of impaired TE (≤1 year relative risk [RR] 1.48, 95% confidence interval [CI] 1.08-2.03; > 1 year: RR 1.58, CI 1.22-2.06) and ER (≤1 year RR 1.51, CI 1.07-2.12; > 1 year RR 1.44, CI 1.06-1.95) versussiblings. Among survivors ≤1 year at diagnosis, treatment with platinum (RR 1.74, CI 1.01-2.97), hearing loss (RR 1.95, CI 1.26-3.00), cardiovascular (RR 1.83, CI 1.15-2.89) and neurologic (RR 2.00, CI 1.32-3.03) conditions were associated with higher risk of impaired TE. Female sex (RR = 1.54, CI, 1.02-2.33), cardiovascular (RR 1.71, CI 1.08-2.70) and respiratory (RR 1.99, CI 1.14-3.49) conditions were associated with higher risk of impaired ER. Among survivors > 1 year at diagnosis those treated in 1970-79 vs. 1990-99 had 80% higher risk of impaired ER (RR 1.77, CI 1.02-3.06). Hearing loss (RR 1.56 (1.09-2.24), respiratory (RR 2.35, CI 1.60-3.45) and cardiovascular (RR 1.74, CI 1.12-2.69) conditions were associated with higher risk of impaired TE. Conclusions: Adult survivors of neuroblastoma are at-risk for neurocognitive impairment. Differences associated with age at diagnosis, chronic disease and treatment exposures may inform risk-stratified inventions to improve neurocognitive outcomes. Reduced risk in later eras may reflect improved supportive care and knowledge of late effects.

scholarly journals Psychosocial and Neurocognitive Outcomes in Adult Survivors of Adolescent and Early Young Adult Cancer: A Report From the Childhood Cancer Survivor Study

2015 ◽  
Vol 33 (23) ◽  
pp. 2545-2552 ◽  
Author(s):  
Pinki K. Prasad ◽  
Kristina K. Hardy ◽  
Nan Zhang ◽  
Kim Edelstein ◽  
Deokumar Srivastava ◽  
...  
Keyword(s):  
Childhood Cancer ◽  
Cancer Survivor ◽  
Emotional Regulation ◽  
Adult Survivors ◽  
Brief Symptom Inventory ◽  
Childhood Cancer Survivor ◽  
Logistic Regression Models ◽  
Childhood Cancer Survivor Study ◽  
Employment Education ◽  
Task Efficiency

Purpose To characterize psychological and neurocognitive function in long-term cancer survivors diagnosed during adolescence and early young adulthood (AeYA). Methods Six thousand one hundred ninety-two survivors and 390 siblings in the Childhood Cancer Survivor Study completed the Brief Symptom Inventory-18 and a Neurocognitive Questionnaire. Treatment and demographic predictors were examined, and associations with social attainment (employment, education, and living independently) were evaluated. Logistic regression models were used to compute odds ratios (ORs) and corresponding 95% CIs. Results Among survivors, 2,589 were diagnosed when AeYA (11 to 21 years old). Adjusted for current age and sex, these survivors, compared with siblings, self-reported higher rates of depression (11.7% v 8.0%, respectively; OR, 1.55; 95% CI, 1.04 to 2.30) and anxiety (7.4% v 4.4%, respectively; OR, 2.00; 95% CI, 1.17 to 3.43) and more problems with task efficiency (17.2% v 10.8%, respectively; OR, 1.72; 95% CI, 1.21 to 2.43), emotional regulation (19.1% v 14.1%, respectively; OR, 1.74; 95% CI, 1.26 to 2.40), and memory (25.9% v 19.0%, respectively; OR, 1.44; 95% CI, 1.09 to 1.89). Few differences were noted between survivors diagnosed with leukemia or CNS tumor before 11 years old versus during later adolescence, although those diagnosed with lymphoma or sarcoma during AeYA were at reduced risk for self-reported psychosocial and neurocognitive problems. Unemployment was associated with self-reports of impaired task efficiency (OR, 2.93; 95% CI, 2.28 to 3.77), somatization (OR, 2.29; 95% CI, 1.77 to 2.98), and depression (OR, 1.94; 95% CI, 1.43 to 2.63). Conclusion We demonstrated that risk for poor functional outcome is not limited to survivors' diagnoses in early childhood. AeYA is a critical period of development, and cancer during this period can impact neurocognitive and emotional function and disrupt vocational attainment.

scholarly journals Co-Deregulated miRNA Signatures in Childhood Central Nervous System Tumors: In Search for Common Tumor miRNA-Related Mechanics

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3028
Author(s):  
George I. Lambrou ◽  
Apostolos Zaravinos ◽  
Maria Braoudaki
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cns Tumors ◽  
Normal Brain ◽  
Cns Tumor ◽  
Different Types ◽  
Receiver Operator Curve Analysis ◽  
The Central Nervous System ◽  
Tumor Types ◽  
Operator Curve

Despite extensive experimentation on pediatric tumors of the central nervous system (CNS), related to both prognosis, diagnosis and treatment, the understanding of pathogenesis and etiology of the disease remains scarce. MicroRNAs are known to be involved in CNS tumor oncogenesis. We hypothesized that CNS tumors possess commonly deregulated miRNAs across different CNS tumor types. Aim: The current study aims to reveal the co-deregulated miRNAs across different types of pediatric CNS tumors. Materials: A total of 439 CNS tumor samples were collected from both in-house microarray experiments as well as data available in public databases. Diagnoses included medulloblastoma, astrocytoma, ependydoma, cortical dysplasia, glioblastoma, ATRT, germinoma, teratoma, yoc sac tumors, ocular tumors and retinoblastoma. Results: We found miRNAs that were globally up- or down-regulated in the majority of the CNS tumor samples. MiR-376B and miR-372 were co-upregulated, whereas miR-149, miR-214, miR-574, miR-595 and miR-765 among others, were co-downregulated across all CNS tumors. Receiver-operator curve analysis showed that miR-149, miR-214, miR-574, miR-595 and miR765 could distinguish between CNS tumors and normal brain tissue. Conclusions: Our approach could prove significant in the search for global miRNA targets for tumor diagnosis and therapy. To the best of our knowledge, there are no previous reports concerning the present approach.

scholarly journals PATH-11. PROSPECTIVE (EPI-)GENETIC CLASSIFICATION OF > 1,000 PEDIATRIC CNS TUMORS—THE MNP 2.0 STUDY

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii426-iii426
Author(s):  
Dominik Sturm ◽  
Felix Sahm ◽  
Felipe Andreiuolo ◽  
David Capper ◽  
Marco Gessi ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Gene Panel ◽  
Cns Tumors ◽  
Lower Grade ◽  
High Grade ◽  
Sequencing Data ◽  
Cns Tumor ◽  
Gene Panel Sequencing ◽  
Tumor Entities ◽  
Panel Sequencing

Abstract The large variety of CNS tumor entities affecting children and adolescents, some of which are exceedingly rare, results in very diverging patient outcomes and renders accurate diagnosis challenging. To assess the diagnostic utility of routine DNA methylation-based CNS tumor classification and gene panel sequencing, the Molecular Neuropathology 2.0 study prospectively integrated these (epi-)genetic analyses with reference neuropathological diagnostics as an international trial for newly-diagnosed pediatric patients. In a four-year period, 1,215 patients with sufficient tissue were enrolled from 65 centers, receiving a reference neuropathological diagnosis according to the WHO classification in &gt;97%. Using 10 FFPE sections as input, DNA methylation analysis was successfully performed in 95% of cases, of which 78% with sufficient tumor cell content were assigned to a distinct epigenetic tumor class. The remaining 22% did not match any of 82 represented classes, indicating novel rare tumor entities. Targeted gene panel sequencing of &gt;130 genes performed for 96% of patients with matched blood samples detected diagnostically, prognostically, or therapeutically relevant somatic alterations in 48%. Germline DNA sequencing data indicated potential predisposition syndromes in ~10% of patients. Discrepant results by neuropathological and epigenetic classification (29%) were enriched in histological high-grade gliomas and implicated clinical relevance in 5% of all cases. Clinical follow-up suggests improved survival for some patients with high-grade glioma histology and lower-grade molecular profiles. Routine (epi-)genetic profiling at the time of primary diagnosis adds a valuable layer of information to neuropathological diagnostics and will improve clinical management of CNS tumors.

Psychometric Validation of the PERMA-Profiler as a Well-Being Measure for Young Adult Survivors of Pediatric Central Nervous System Tumor

2021 ◽  
pp. 003435522110255
Author(s):  
Teresa Ann Grenawalt ◽  
Emre Umucu ◽  
Antonio Reyes ◽  
Andrea Baylin ◽  
David R. Strauser ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Factor Analysis ◽  
Young Adult ◽  
Concurrent Validity ◽  
Adult Survivors ◽  
Well Being ◽  
Psychometric Validation ◽  
Cns Tumor ◽  
Young Adult Survivors

This study aims to validate a measure of well-being, the PERMA-Profiler, among a sample of young adult survivors of pediatric central nervous system (CNS) tumor. Measurement structure of the PERMA-Profiler was evaluated using exploratory factor analysis and confirmatory factor analysis using pretest–posttest data. Reliability and concurrent validity of the PERMA-Profiler were examined. This study included 127 young adult survivors of pediatric CNS tumor between the ages of 18 and 30 ( M = 23.83, SD = 3.00) years. The results of factor analyses yielded a single-factor solution for well-being. Significant relationships between well-being and happiness, life satisfaction, perceived stress, and physical health were observed, providing support for the concurrent validity of the PERMA-Profiler. The PERMA-Profiler displayed good internal consistency and test–retest reliability. The PERMA-Profiler can help rehabilitation researchers and counselors better evaluate well-being in young adult survivors of pediatric CNS tumor, which provides opportunity for more targeted psychosocial interventions.

scholarly journals Promoting Conversations About Cognitive Decline Between Older Adults and Primary Care Providers

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 157-158
Author(s):  
Benjamin Olivari ◽  
Christopher Taylor ◽  
Nia Reed ◽  
Lisa McGuire
Keyword(s):  
Alzheimer’S Disease ◽  
Primary Care ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Cognitive Decline ◽  
Chronic Conditions ◽  
Memory Loss ◽  
Primary Care Providers ◽  
Subjective Cognitive Decline ◽  
Care Providers

Abstract Alzheimer’s disease and related dementias often begin with symptoms of mild memory loss, eventually leading to more severe cognitive impairment, functional impairment, and ultimately, death. Data from the Behavioral Risk Factor Surveillance System core questions related to chronic diseases and from the cognitive decline optional module on subjective cognitive decline (SCD) from the years 2015-2018 were aggregated across the participating 50 states, D.C., and Puerto Rico for this analysis. Among U.S. adults aged 65 years and older, only 39.8% (95%CI=37.6-42.1) of those experiencing SCD reported discussing their SCD symptoms with a healthcare provider. The prevalence of discussing SCD symptoms with a provider was higher among those with at least one chronic condition than among those with no chronic conditions. 30.7% (28.6-32.8) of those aged 65 years and older reported that their SCD led to functional limitations and 28.8% (26.5-31.2) needed assistance with day-to-day activities. For patients aged 65 years and older, Welcome to Medicare visits and Medicare Annual Wellness Visits are critically underutilized primary care access points. Primary care providers can manage chronic conditions, cognitive health, and initiate referrals for testing. Efforts to promote the use of toolkits and diagnostic codes that are available to primary care providers to initiate conversations about memory loss with patients may be utilized to improve detection, diagnosis, and planning for memory problems. Discussions may lead to earlier detection and diagnosis of cognitive impairment, such as Alzheimer’s disease, or other treatable conditions such as delirium or pressure in the brain and avoid costly hospitalizations.

scholarly journals Long-term medical imaging use in children with central nervous system tumors

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0248643
Author(s):  
Erin J. A. Bowles ◽  
Diana L. Miglioretti ◽  
Marilyn L. Kwan ◽  
Ute Bartels ◽  
Adam Furst ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Medical Imaging ◽  
Tumor Grade ◽  
Tumor Diagnosis ◽  
Cns Tumors ◽  
Cns Tumor ◽  
Longitudinal Imaging ◽  
The U.S

Background Children with central nervous system (CNS) tumors undergo frequent imaging for diagnosis and follow-up, but few studies have characterized longitudinal imaging patterns. We described medical imaging in children before and after malignant CNS tumor diagnosis. Procedure We conducted a retrospective cohort study of children aged 0–20 years diagnosed with CNS tumors between 1996–2016 at six U.S. integrated healthcare systems and Ontario, Canada. We collected computed topography (CT), magnetic resonance imaging (MRI), radiography, ultrasound, nuclear medicine examinations from 12 months before through 10 years after CNS diagnosis censoring six months before death or a subsequent cancer diagnosis, disenrollment from the health system, age 21 years, or December 31, 2016. We calculated imaging rates per child per month stratified by modality, country, diagnosis age, calendar year, time since diagnosis, and tumor grade. Results We observed 1,879 children with median four years follow-up post-diagnosis in the U.S. and seven years in Ontario, Canada. During the diagnosis period (±15 days of diagnosis), children averaged 1.10 CTs (95% confidence interval [CI] 1.09–1.13) and 2.14 MRIs (95%CI 2.12–2.16) in the U.S., and 1.67 CTs (95%CI 1.65–1.68) and 1.86 MRIs (95%CI 1.85–1.88) in Ontario. Within one year after diagnosis, 19% of children had ≥5 CTs and 45% had ≥5 MRIs. By nine years after diagnosis, children averaged one MRI and one radiograph per year with little use of other imaging modalities. Conclusions MRI and CT are commonly used for CNS tumor diagnosis, whereas MRI is the primary modality used during surveillance of children with CNS tumors.

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